Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease.
Analysis of recently identified dyslipidemia alleles reveals two loci that contribute to risk for carotid artery disease.
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DOI：
10.1186/1476-511x-8-52
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发表时间：
2009-12-01
影响因子：
4.5
通讯作者：
Jarvik GP
中科院分区：
文献类型：
--
作者：
Ronald J;Rajagopalan R;Ranchalis JE;Marshall JK;Hatsukami TS;Heagerty PJ;Jarvik GP
全基因组关联研究已经确定了许多影响高密度脂蛋白（HDL）或低密度脂蛋白（LDL）胆固醇水平的单核苷酸多态性（SNP）;这些SNP可能有助于血管疾病的遗传基础。我们在病例对照队列中评估了23个位点的34个SNP对血脂异常、关键脂质亚表型和严重颈动脉疾病（CAAD）的影响。这些SNPs对HDL和LDL的影响与先前报道的一致，我们提供了由遗传风险评分解释的HDL（3.9%）和LDL（3.3%）方差百分比的无偏估计。我们评估了这些SNP对HDL亚组分、载脂蛋白A-1、LDL浮力、载脂蛋白B和脂蛋白（a）的影响，发现rs646776预测载脂蛋白B水平，而rs 2075650预测LDL浮力。最后，我们测试了这些SNP在超声记录的CAAD狭窄状态风险中的作用。我们发现CELSR 2和PSRC 1附近的1p13.3和TOMM 40附近的19q13.2以及APOE附近的rs 2075650两个位点存在CAAD的危险等位基因。我们分析了23个位点的34个导致血脂异常的SNP，结果表明1p13.3区域的遗传变异可能通过增加LDL颗粒数量来增加CAAD的风险，而19q13.2区域的变异可能通过促进更小、更密集的LDL颗粒的形成来增加CAAD的风险。
Genome-wide association studies have identified numerous single nucleotide polymorphisms (SNPs) affecting high density lipoprotein (HDL) or low density lipoprotein (LDL) cholesterol levels; these SNPs may contribute to the genetic basis of vascular diseases. We assessed the impact of 34 SNPs at 23 loci on dyslipidemia, key lipid sub-phenotypes, and severe carotid artery disease (CAAD) in a case-control cohort. The effects of these SNPs on HDL and LDL were consistent with those previously reported, and we provide unbiased estimates of the percent variance in HDL (3.9%) and LDL (3.3%) explained by genetic risk scores. We assessed the effects of these SNPs on HDL subfractions, apolipoprotein A-1, LDL buoyancy, apolipoprotein B, and lipoprotein (a) and found that rs646776 predicts apolipoprotein B level while rs2075650 predicts LDL buoyancy. Finally, we tested the role of these SNPs in conferring risk for ultrasonographically documented CAAD stenosis status. We found that two loci, chromosome 1p13.3 near CELSR2 and PSRC1 which contains rs646776, and 19q13.2 near TOMM40 and APOE which contains rs2075650, harbor risk alleles for CAAD. Our analysis of 34 SNPs contributing to dyslipidemia at 23 loci suggests that genetic variation in the 1p13.3 region may increase risk of CAAD by increasing LDL particle number, whereas variation in the 19q13.2 region may increase CAAD risk by promoting formation of smaller, denser LDL particles.